The dextrorotatory enantiomer (Structure 1), bearing the International Non-Proprietary name Clopidogrel, has the absolute configuration S and is a commercially significant drug with antithrombic and platelet aggregation inhibiting activity as disclosed in U.S. Pat. No. 4,847,265. Similar properties are disclosed in U.S. Pat. No. 4,529,596.

Structure 2, known as Ticlopidine, is an antithrombotic drug with platelet aggregation inhibiting properties as disclosed in U.S. Pat. No. 4,051,141 and U.S. Pat. No. 4,127,580.

The synthesis of Ticlopidine is described in Heterocycles, 1979, 12, 1479 and in FR Pat. 2,424,278. A final step towards Ticlopidine involves the dehydroxylation of hydroxyl precursor 3 (R=H) with SnCl2/HCl reagent (Scheme 1). This reagent has also been applied towards the synthesis of Clopidogrel (R=COOCH3). (U.S. Pat. No. 6,495,691).

Enormous difficulties exist for using SnCl2 in this type of transformation especially when considering large scale reactions. The main problem consists of removing the tin byproducts after completion of the reaction. In our experience, from laboratory scale reactions, an aqueous work-up of the reaction results in the formation of persistent emulsions. This would result in increased processing time particularly on scale-up to achieve phase separations. Emulsions are very problematic on scale-up and need to be avoided in commercial production of pharmaceuticals and fine chemicals (see Practical Process Research & Development, by Anderson, N. G., Academic Press, 2000, pages 323–324). Furthermore, the possibility of tin contamination in the final product exists. Therefore, it would be very difficult to meet the high purity specifications required for a pharmaceutical product. Consequently, a method that would not suffer from the disadvantages of the prior art was required.
It is therefore an object of the present invention to provide an improved process for the preparation of racemic and/or enantiomerically enriched 4,5,6,7-tetrahydrothieno[3,2-c]pyridines with inexpensive reagents and which avoids the problems encountered with the SnCl2/HCl reagent (i.e. work-up and isolation of product).